Allergy to rocuronium: from clinical suspicion to correct diagnosis.

BACKGROUND: Allergy to rocuronium can be life-threatening. Correct diagnosis is a prerequisite because of serious consequences of diagnostic error. OBJECTIVE: To assess skin testing, quantification of specific IgE (sIgE) and flow-assisted activation of basophils [basophil activation test (BAT)] in the diagnosis of rocuronium allergy. METHODS: This study comprises 104 curarized patients with a history of profound hypotension and severe bronchospasm immediately after induction of anaesthesia. All patients had skin tests, quantification of sIgE and BAT to rocuronium, together with investigations for all relevant compounds administered during anaesthesia that could have evoked the reaction. Diagnosis of rocuronium allergy was considered definite when the patient demonstrated a positive outcome for at least two of the three aforementioned tests. RESULTS: The positive predictive value for skin testing, BAT and sIgE was 98% (CI 95%: 92-99%), 97% (CI 95%: 88-100%) and 83% (CI 95%: 74-89%), respectively. The negative predictive value for skin testing, BAT and sIgE was 96% (CI 95%: 86-99%), 75% (CI 95%: 67-75%) and 72% (CI 95%: 58-83%), respectively. Cross-reactivity with vecuronium was documented in 69% of the patients. CONCLUSION: Skin testing merits the status of primary diagnostic investigation to document rocuronium allergy and cannot be substituted by quantification of sIgE or BAT. SIgE can offer a diagnostic advantage in cases where skin tests yield negative results. However, additional tests (e.g. BAT) are of capital importance in patients with negative skin tests and positive sIgE results to help in interpreting the clinical significance of a positive sIgE result. Optimal assessment of cross-reactivity between rocuronium and vecuronium implies both skin testing and BAT.

Pre- and post-natal exposure to antibiotics and the development of eczema, recurrent wheezing and atopic sensitization in children up to the age of 4 years.

BACKGROUND: Little data are available on the relationship between indirect antibiotic exposure of the child in utero or during lactation and allergic diseases. On the other hand, several studies have been conducted on the association with direct post-natal antibiotic exposure, but the results are conflicting. OBJECTIVE: The aim of this study was to investigate pre- and post-natal antibiotic exposure and the subsequent development of eczema, recurrent wheeze and atopic sensitization in children up to the age of 4 years. METHODS: We conducted an aetiologic study in 773 children based on a prospective birth cohort project in which environmental and health information were collected using questionnaires. Antibiotic exposure was assessed as maternal antibiotic intake during pregnancy and during lactation and as medication intake of the child. The chronology of exposures and outcomes was taken into account during the data processing. At the age of 1 and 4 years, a blood sample was taken for the quantification of specific IgE. RESULTS: Prenatal antibiotic exposure was significantly positively associated with eczema, whereas no association was found with recurrent wheeze and atopic sensitization. We found a positive, although statistically not significant, association between antibiotic exposure through breastfeeding and recurrent wheeze. Neither eczema nor atopic sensitization was significantly associated with antibiotic exposure through breastfeeding. Finally, we observed a negative association between the use of antibiotics in the first year of life and eczema and atopic sensitization, and also between antibiotic use after the first year of life and recurrent wheeze, eczema and atopic sensitization. CONCLUSION: Indirect exposure to antibiotics (in utero and during lactation) increases the risk for allergic symptoms in children, while direct exposure to antibiotics appears to be protective. The biological mechanisms underlying these findings still need to be elucidated.

Perinatal risk factors for sensitization, atopic dermatitis and wheezing during the first year of life (PIPO study).

OBJECTIVE: To evaluate the influence of perinatal environmental factors on early sensitization, atopic dermatitis and wheezing during the first year. METHODS: Information on pregnancy-related factors, parental atopic history, environmental factors and the clinical course of the infant until age one was gathered by questionnaires, as part of a prospective birth cohort study (Prospective study on the Influence of Perinatal factors on the Occurrence of asthma and allergies [PIPO-study]). Quantification of total and specific IgE was performed in 810 children and their parents. RESULTS: Early sensitization was found in 107/810 (13%) of the infants. Multiple regression analysis showed that specific IgE in fathers was a risk factor for early sensitization in their daughters (adjusted odds ratios (OR(adj)) 2.21 (95% confidence interval (CI) 1.10-4.49); P=0.03), whereas in boys, day care attendance was shown to be protective for early sensitization (OR(adj) 0.38 (95% CI 0.20-0.71); P=0.001). Atopic dermatitis occurred in 195/792 infants (25%). Specific IgE in the mother (OR(adj) 1.52 (95% CI 1.06-2.19); P=0.02) and in the infant (OR(adj) 4.20 (95% CI 2.63-6.68); P<0.001) were both risk factors for the occurence of atopic dermatitis, whereas postnatal exposure to cats was negatively associated with atopic dermatitis (OR(adj) 0.68 (0.47-0.97); P=0.03). Postnatal exposure to cigarette smoke (OR(adj) 3.31 (95% CI 1.79-6.09); P<0.001) and day care attendance (OR(adj) 1.96 (95% CI 1.18-3.23); P=0.009) were significantly associated with early wheezing, which occurred in 25% (197/795) of the infants. CONCLUSION: The effect of paternal sensitization and day care attendance on sensitization is gender dependent. Maternal sensitization predisposes for atopic dermatitis, whereas postnatal exposure to cats had a protective effect.

Changes in respiratory and allergic symptoms in schoolchildren from 1996 to 2002, results from the ISAAC surveys in Antwerp (Belgium).

Two cross sectional surveys (1995/1996 and 2001/2002) were carried out according to the ISAAC protocol among 6-7 and 13-14 year old schoolchildren in Antwerp, Belgium. A total of 8244 children participated in 1996 and 8159 children in 2002. No significant differences in current prevalence of asthma and asthma medication was found in 6-7 year olds and 13-14 year old girls. Significantly less asthma and asthma medication was reported by 13-14 year old boys in 2002. Symptoms of wheeze had lower occurrence in all groups in 2002, which was significant for older age group. Current prevalence of rash was significantly higher in the 6-7 year olds in 2002. No such increase was found for rash in the older age groups but they reported significantly more rhinitis. No differences were found between urban and suburban Antwerp in either survey. No clear changes in the occurrence of asthma were found for school children in Antwerp while wheeze was reported less in 2002 compared to 1996. Allergic disorders had higher occurrences in schoolchildren in 2002.

Comparative analysis of the biochemical and immunohistochemical determination of hormone receptors in invasive breast carcinoma influence of the tumor-stroma ratio.

Tumor samples obtained from 106 primary breast cancer patients were examined biochemically (DCCA) and immunohistochemically (IHC) for estrogen (ER) and progesterone receptors (PR) to assess a quantitative relationship between both assays and to study the influence of the tumor-stroma ratio on this quantitative relationship. We used a model of logit transformation of IHC values (% of positive cells) and logarithmic transformation of DCCA values (fmol receptor/mg cytosolic protein). Tumors were subdivided into three categories according to the tumor-stroma ratio (more (t > s), equal amounts (t = s) or less (t < s) tumor than stroma), and the influence of the tumor-stroma ratio was studied using multiple regression analysis. We report a mathematical relationship between the results of the biochemical and immunohistochemical assays for the determination of ER status and PR status in primary breast cancer patients (ER: log DCCA(fmol/mg) = 0.369 logit (IHC(%pos cells)) + 2.328 (r = 0.573; p < 0.0001); PR: log DCCA (fmol/mg) = 0.474 logit (IHC(%pos cells)) + 0, 00 (r = 0.634; p < 0.0001)). In tumors overexpressing ER immunohistochemically (>10% nuclear positivity), median ER-DCCA is significantly higher if the tumor-stroma ratio is greater than 1. As these patients respond to hormonal treatment, depending on the degree of expression of both receptors, this study suggests that the biochemical assay be avoided because this technique is hampered by false-negative or falsely low results due to the loss of morphological information on the tumor-stroma ratio.

Deep venous thrombosis after laparoscopic cholecystectomy and prevention with nadroparin.

BACKGROUND: Postoperative thromboembolic disease has been suggested to occur with higher frequency during laparoscopic cholecystectomy than during other laparoscopic procedures or conventional cholecystectomy. The aim of this prospective study was to evaluate the occurrence of deep vein thrombosis (DVT) in laparoscopic cholecystectomy patients, whether they were treated with low-molecular-weight heparins or not. METHODS: All 238 laparoscopic cholecystectomy patients included in the study underwent pre- and postoperative venous duplex scanning of both legs. Subcutaneous Nadroparin was administred to 105 patients. The remaining 133 patients did not receive pharmacologic prophylaxis. The different risk factors for thromboembolic disease were distributed evenly between the two groups, except for the duration of general anesthesia. RESULTS: No patient had postoperative clinical manifestations of DVT or pulmonary embolism. In five patients, DVT was detected at duplex scan approximately 10 days after surgery. Four DVTs were found among the 133 patients who did not receive Nadroparin (1.68%). In the group with pharmacologic prevention, one patient manifested a DVT (0.42%), giving a total DVT incidence of 2.10% after laparoscopic cholecystectomy. The difference between the two groups was not significant (p = 0.27), but the results seem to indicate a tendency toward a lower incidence in the Nadroparine group. CONCLUSIONS: In the light of the study results, it seems advisable to use thromboembolic prophylaxis during laparoscopic cholecystectomy.

Beta-cell, thyroid, gastric, adrenal and coeliac autoimmunity and HLA-DQ types in type 1 diabetes.

The autoimmune attack in type 1 diabetes is not only targeted to beta cells. We assessed the prevalence of thyroid peroxidase (aTPO), parietal cell (PCA), antiadrenal (AAA) and endomysial antibodies (EmA-IgA), and of overt autoimmune disease in type 1 diabetes, in relation to gender, age, duration of disease, age at onset, beta-cell antibody status (ICA, GADA, IA2A) and HLA-DQ type. Sera from 399 type 1 diabetic patients (M/F: 188/211; mean age: 26 +/- 16 years; duration: 9 +/- 8 years) were tested for ICA, PCA, AAA and EmA-IgA by indirect immunofluorescence, and for IA2A (tyrosine phosphatase antibodies), GADA (glutamic acid decarboxylase-65 antibodies) and aTPO by radiobinding assays. The prevalence rates were: GADA 70%; IA2A, 44%; ICA, 39%; aTPO, 22%; PCA, 18%; EmA-IgA, 2%; and AAA, 1%. aTPO status was determined by female gender (beta = - 1.15, P = 0.002), age (beta = 0.02, P = 0.01) and GADA + (beta = 1.06, P = 0.02), but not by HLA-DQ type or IA2A status. Dysthyroidism (P < 0.0001) was more frequent in aTPO + subjects. PCA status was determined by age (beta = 0.03, P = 0.002). We also observed an association between PCA + and GADA + (OR = 1.9, P = 0.049), aTPO + (OR = 1.9, P = 0.04) and HLA DQA1*0501-DQB1*0301 status (OR = 2.4, P = 0.045). Iron deficiency anaemia (OR = 3.0, P = 0.003) and pernicious anaemia (OR = 40, P < 0.0001) were more frequent in PCA + subjects. EmA-IgA + was linked to HLA DQA1*0501-DQB1*0201 + (OR = 7.5, P = 0.039), and coeliac disease was found in three patients. No patient had Addison's disease. In conclusion, GADA but not IA2A indicate the presence of thyrogastric autoimmunity in type 1 diabetes. aTPO have a female preponderance, PCA are weakly associated with HLA DQA1*0501-DQB1*0301 and EmA-IgA + with HLA DQA1*0501-DQB1*0201.

Increased occurrence of asthma and allergy: critical appraisal of studies using allergic sensitization, bronchial hyper-responsiveness and lung function measurements.

BACKGROUND: Many studies have reported an increase in the occurrence of asthma and respiratory allergies in recent decades, but this increase is mostly based on studies using rather subjective measurements of asthma and allergies, such as questionnaires and doctor's diagnosis. None of the reviews specifically focused on studies using more 'objective' measurements, such as sensitization (specific IgE or skin prick testing (SPT)), bronchial hyper-responsiveness (BHR) or lung function (LF). OBJECTIVE: To review articles studying a time trend of occurrence of these 'more objective' measurements. METHODS: A MEDLINE-search (1966-February 2000) was performed. The following criteria were used: population-based, using IgE, SPT, BHR or LF measurements in the same age-group at least twice, with at least 2 years between and using similar methods. RESULTS: The MEDLINE-search resulted in only 16 articles, performed in 13 populations in seven different countries. Nine articles used the same objective measurements twice in the whole population. Three of these reported a non-significant increase or decrease. The other six articles found a significant increase in at least one objective measurement and of these only three reported a consistent significant increase. CONCLUSIONS: The increase in the occurrence of reported asthma and allergy is supported by only a few articles confirming these results with 'more objective measurements'.

The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and angiogenesis) in invasive cervical cancer.

OBJECTIVE: The present study was designed to analyse the relationship between apoptosis related proteins (bcl-2 and bax), tumour suppressor protein p53, proliferation markers (PCNA and mitotic index), human papillomavirus (HPV) and angiogenesis in cervical cancer and their impact on clinical outcome. STUDY DESIGN: Tumours from 111 patients were assessed by immunohistochemistry for the expression of bcl-2, bax, p53 and PCNA, by PCR for the presence of HPV-DNA, for the quantification of the mitotic index and the microvessel density (CD 31). The results were correlated with various histopathologic characteristics and survival. RESULTS: The multiple Cox's regression analysis for overall survival of all prognostic variables gave as best model: bcl-2 (P<0.001), lymphovascular permeation (P=0.004), mitotic index (P=0.019), tumour grade (P=0.048) and FIGO stage (P=0.070). Subanalysis was performed for the patients where the lymph node status was known (n=79). Adding the lymph node status gave as best model for overall survival bcl-2 (P=0.001), lymphovascular permeation (P=0.003) and mitotic index (P=0.044). However, they hardly influenced the association. CONCLUSION: In the apoptotic pathway of cervical cancer, bcl-2 is one of most important proteins. It can probably not only mediate cell death but also regulate cell growth. A better understanding of their relations will probably provide the basis for more rational cancer therapies in the future.

Higher occurrence of asthma-related symptoms in an urban than a suburban area in adults, but not in children.

In young adults, a higher occurrence of asthma-related symptoms was found in an urban than an adjacent suburban area in a survey performed in 1991. The authors now wondered whether such differences could be established in other age groups. The present study (in 1996) included 14,299 subjects, aged 5-75 yrs, of a random sample of the general population in the same two adjacent areas: the centre of Antwerp (Belgium) and its south suburban border. The standardized European Community Respiratory Health Survey (ECRHS) and International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires were used to assess the occurrence of asthma-related symptoms. Higher rates were confirmed in urban compared to suburban Antwerp in adults (20-75 yrs), but no such area differences were found in children (5-8 and 12-15 yrs). Adjustment for a number of recorded risk factors did not seem to affect the area differences in asthma-related symptoms. Comparing the survey results of 1991 and 1996 in 20-44 yr old adults, the findings suggest a slight increase in reported respiratory symptoms in both areas. A higher occurrence of asthma symptoms was observed in the urban than suburban area in adults, but not in children. This might be explained by a progressive effect of long-term exposure to the "urban environment". However, longitudinal studies are necessary to further clarify the factors accounting for these age-related area differences.

The role of surgery in invasive squamous carcinoma of the vagina.

OBJECTIVE: The aim of this study was to define the role of surgery in managing patients with a primary squamous vaginal cancer. METHODS: A retrospective review was conducted of patients with primary invasive vaginal cancer managed at one institution over a 25-year period. The results were compared with those of all major publications of the past 20 years. RESULTS: A total of 84 patients were reviewed. Forty-five (66%) were of squamous origin. The median follow-up was 45 months (range: 0.6-268). The patients were primarily treated by surgery in 67% and by radiotherapy alone in 33% of cases. The 5- and 10-year overall survival was, respectively, 74 and 58%. For stage I the figures were 91 and 70%. These survival rates compared favorably with those of published series of cases managed by radiotherapy alone. Univariate analysis showed that age (P = 0.004), size (P = 0.009), site (P = 0.016), lymph node status (P = 0.022), FIGO stage (P = 0.027), and treatment (P = 0.003) were relevant prognostic factors. Multiple regression analysis, however, revealed that only age (P = 0.009) and size (P = 0.037) were independent prognostic variables. CONCLUSIONS: Stage I and II squamous vaginal cancer patients have good outcomes in terms of survival and local tumor control if they are managed by initial surgery followed by selective radiotherapy.

Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease?

BACKGROUND: One of the mechanisms evoked to explain the increasing prevalences of asthma and allergy, in particular among children, is the 'Western lifestyle' or 'hygiene' hypothesis. As early childhood infections are assumed to hold a protective effect on the development of asthma and allergies, the use of antibiotics at that sensitive age may lead to an increased risk of asthma and allergy. OBJECTIVE: The aim of this study is to investigate the association between the use of antibiotics in the first year of life and the subsequent development of asthma and allergic disorders. METHODS: In a population-based sample of 7-and-8-year-old children questionnaire and skin prick test data were collected from 1206 and 675 subjects, respectively. Prevalence rates of asthma, allergic disorders and skin test positivity were compared between children with and without early life use of antibiotics, taking into account other possible risk factors including early respiratory infections. The effect of genetic predisposition was investigated by stratified analyses of children with and without parental hay fever. RESULTS: The use of antibiotics during the first year of life was significantly associated with asthma (OR = 1.7, 95% CI 1.0-3.1), hay fever (OR = 2.3, 95% CI 1.3-3.8) and eczema (OR = 1.3, 95% CI 1.0-1.8). No significant relationship was found with skin test positivity (OR = 1.1, 95% CI 0.7-1.7). After stratification for the presence of parental hay fever, children without parental hay fever did not show any significant associations between antibiotics use and asthma or allergy, whereas in children with parental hay fever the use of antibiotics was significantly related with asthma (OR = 2.3, 95% CI 1.1-5.1), hay fever (OR = 2.8, 95% CI 1.5-5.1) and eczema (OR = 1.6, 95% CI 1.0-2.6), and of borderline statistical significance with skin test positivity (OR = 1.6, 95% CI 0.9-3.0). CONCLUSION: Early childhood use of antibiotics is associated with an increased risk of developing asthma and allergic disorders in children who are predisposed to atopic immune responses. These findings support recent immunological understanding of the maturation of the immune system.

Long-term effects of specific immunotherapy, administered during childhood, in asthmatic patients allergic to either house-dust mite or to both house-dust mite and grass pollen.

In a retrospective study, asthmatic patients allergic to either house-dust mite (HDM) (Dermatophagoides pteronyssinus) (n = 34) or to both HDM and grass pollen (GP) (n = 14), and who were treated with specific immunotherapy (SIT) during childhood (mean duration of SIT: 61 +/- 9.70 months), were re-evaluated in early adulthood after mean cessation of SIT for 9.3 +/- 2.76 years. The results were compared to those of a control group of asthmatic patients (n = 42) with comparable asthma features, who were treated with appropriate antiasthmatic drugs during childhood, but who never received SIT. Re-evaluation was carried out with a standardized questionnaire, skin prick tests (SPT), and lung-function assessments. At the time of re-evaluation, the mean age in the SIT-treated group was 23.1 +/- 3.50 years; in the control group, it was 22.7 +/- 3.40 years. At re-evaluation, the risk of frequent asthmatic symptoms was three times higher in the control group than in the SIT-treated group (prevalence ratio: 3.43; P = 0.0006). The frequent use of antiasthmatic medication was also more pronounced in the control group, although the difference was not statistically significant (P=0.38). Lung-function parameters and results of SPT with HDM were comparable in both groups. It is concluded that SIT has long-term effects on asthmatic symptoms in young adults.

Occupational risk factors of lung cancer: a hospital based case-control study.

OBJECTIVES: To investigate the relation between lung cancer and exposure to occupational carcinogens in a highly industrialised region in western Europe. METHODS: In a case-control study 478 cases and 536 controls, recruited from 10 hospitals in the Antwerp region, were interviewed. Cases were male patients with histologically confirmed lung cancer; controls were male patients without cancer or primary lung diseases. Data were collected by questionnaires to obtain information on occupations, exposures, and smoking history. Job titles were coded with the Office of Populations, Censuses and Surveys industrial classification. Exposure was assessed by self report and by job-task exposure matrix. Exposure odds ratios were calculated with logistic regression analysis adjusted for age, smoking history, and marital and socio-economic status. RESULTS: A job history in the categories manufacturing of transport equipment other than automobiles (for example, shipyard workers), transport support services (for example, dockers), and manufacturing of metal goods (for example, welders) was significantly associated with lung cancer (odds ratios (ORs) 2.3, 1.6, and 1.6 respectively). These associations were independent of smoking, education, civil, and economic status. Self reported exposure to potential carcinogens did not show significant associations with lung cancer, probably due to nondifferential misclassification. When assessed by job-task exposure matrix, exposure to molybdenum, mineral oils, and chromium were significantly associated with lung cancer. A strong association existed between smoking and lung cancer: OR of ex-smokers 4.2, OR of current smokers 14.5 v non-smokers. However, smoking did not confound the relation between occupational exposure and lung cancer. CONCLUSIONS: The study has shown a significant excess risk of lung cancer among workers in manufacturing of metal goods, manufacturing of transport equipment (other than automobiles), and transport support services. Assessment of exposure to specific carcinogens resulted in significant associations of chromium, mineral oils, and molybdenum with lung cancer. This study is, to our knowledge, the first study reporting a significant association between occupational exposure to molybdenum and lung cancer.

Does treatment of asthmatic children with inhaled corticosteroids affect their adult height?

In this retrospective study, adult height was assessed in young adult asthmatics who were treated with inhaled corticosteroids (ICs) during childhood (n = 42; 26 boys) and compared to those obtained in asthmatic patients who were never treated with ICs during childhood (n = 43; 23 boys). Standing height of all subjects and their parents was measured. Height data were analyzed using actual length and target height in centimeters, standard deviation scores (SDS), and difference between adult height of the patients and their target height (adult height minus target height). Mean adult height was the same in subjects who took ICs during childhood as compared to those who had never received ICs (boys: 179.3cm+/-6.8 vs. 180.4 cm+/-5.6; girls: 165.8 cm+/-7.5 vs. 167.7 cm+/-7.2). SDS of adult height was also not different between the two groups: in subjects who did not take ICs it was 0.89+/-1.00, while in those who took ICs it was 0.66+/-1.10 (P = 0.31). SDS of target height was also not different between the two groups: in subjects not taking ICs it was 0.95+/-0.86, while in those who took ICs it was 0.28+/-0.76 (P = 0.30). However, subjects who took ICs during childhood showed a statistically significant lower value of adult height minus target height than those who never took ICs (whole group: -0.003+/-5.9 vs. 2.54 +/-4.8, P = 0.03 ; boys: 0.004+/-5.8 vs. 3.09+/-4.5, P = 0.04 ; girls: -0.075+/-6.3 vs. 1.91+/-5.2, P = 0.31). Patients on ICs during childhood who had ever been hospitalized for asthma showed a lower value for adult height minus target height than those who took ICs but were never hospitalized (-3.08+/-7.8 vs. 1.06+/-4.8, P = 0.046). A logistic regression analysis predicting growth impairment showed that the best-fitting model was one that used only ICs as a dependent variable (crude odds ratio, 3.3; 95% CI, 1.3-8.4). Patients who were treated with ICs in combination with intranasal corticosteroids (treatment for rhinitis) tended to have a lower value of adult height minus target height than the other children, but the difference was not statistically significant (P = 0.07). We conclude that although adult height was the same in young adults who were treated with ICs during childhood compared to those who were not treated with ICs during childhood, there was a statistically significant difference between the two groups for adult height minus target height, suggesting mild growth retardation in patients who took ICs during childhood. These findings may be explained by the use of ICs, but it seems more likely that a difference in asthma severity between both groups was responsible for it.

Lung function measures and their relationship to respiratory symptoms in 7- and 8-year-old children.

Abnormal pulmonary function in childhood is a well-known risk factor for lung function impairment in adult life. It is therefore of clinical interest to recognize lower pulmonary function in childhood. We investigated the association between asthma-like respiratory symptoms and the lung function parameters FVC, FEV1, and FEF(25-75) in a population-based sample of 402 schoolchildren, aged 7 and 8 years, using linear regression analyses. Without accounting for other respiratory symptoms, wheeze, exercise-induced wheeze, chronic cough, and history of wheezy bronchitis or lower respiratory infections in early childhood were significantly associated with reduced lung function. After stepwise elimination of symptoms from the regression models, only exercise-induced wheeze (FEV1, -15%pred, FEF(25-75), -21%pred) and a history of chronic cough (FEV1, -5%pred; FEF(25-75), -11%pred) remained significant predictors of decreased lung function. After adjustment for different variability, no significant differences were seen between the effects of symptoms on the flow measurements FEV1 and FEF(25-75). We conclude that children who report exercise-induced wheeze and/or chronic cough may have a considerable deficit in lung function at early school age.

Gender differences in respiratory, nasal and skin symptoms: 6-7 versus 13-14-year-old children.

ISAAC questionnaires were completed by the parents of 6432 children, aged 6-7 y and by themselves by 2864 children 13-14-y-old. Prevalence rates of respiratory and nasal symptoms and a diagnosis of asthma and hay fever were higher in 6-7-y-old boys than in girls, while girls aged 13-14 y had higher rates for most symptoms, except asthma. Underdiagnosis of asthma in 13-14-y-old girls cannot be excluded as an explanation, but our data suggest under-reporting of respiratory and nasal symptoms in 13-14-y-old boys.

Croup and recurrent croup: their association with asthma and allergy. An epidemiological study on 5-8-year-old children.

UNLABELLED: The cumulative incidence (i.e. lifetime prevalence) of croup and recurrent croup (RC) was investigated by questionnaire in a large group (n = 5756) of 5-8-year-old children (mean age: 6.8 +/- 0.6 years) and the risk for asthma and/or wheezing in children with croup and RC assessed. In a random sample of the children, skin prick testing with common inhalant allergens (n = 614) and spirometry (n = 305) were performed and the results were compared between children with or without croup or RC. Of the children, 15.5% had suffered from croup, while 5.0% had had RC. The cumulative incidence was higher in boys than in girls (P < 0.05). In the children with croup or RC an increased risk for wheezing, asthma, usage of anti-asthma medication, rhinitis and hay fever was found (P < 0.01). There was no difference in the prevalence of positive skin prick tests between children with and without croup or RC. Mean percentage predicted forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow was not different between children with and without croup or RC. However, children who had suffered from croup (with or without wheezing) had a lower mean percentage predicted forced expiratory flow at both 50% and 75% of forced vital capacity than those without croup (P = 0.002). A family history of hay fever, chronic bronchitis and eczema was associated with the presence of croup or RC (P < 0.01), while this was hardly the case for a family history of asthma. CONCLUSION: Croup and recurrent croup are associated with bronchial asthma. The association seems essentially based on the presence of hyperreactive airways and less on the presence of atopy, although the latter can be considered an aggravating factor.

Hepatitis B vaccination in mentally retarded: effectiveness after 11 years.

The long-term effectiveness of hepatitis B vaccination was determined in a high-risk group of 105 institutionalized mentally retarded. All individuals were vaccinated in 1986, with three (0, 1, 6 months), four (0, 1, 6 and 12 months) or more doses according to their immune response at month 7, resulting in group 1 (G1), group 2 (G2) and group 3 (G3). They were annually followed up for five years, after which they received a booster dose. Eleven years after the initial vaccination, they were again tested for the presence of hepatitis B virus (HBV) serologic markers. The decline in anti-HBs logtitre over the first five years was 51% for G1 and 45% for G2. From the booster on month 60 to year 11, the overall decline was 31%. Eleven years after the start of vaccination and six years after the booster, 92% of the individuals had protective antibody levels higher than 10 IU/L. G1 had a geometric mean titre of 2015 IU/L, for G2 this was 245 IU/L. The difference in response to vaccination between the groups did not affect their protection. Only two vaccinees seroconverted to anti-HBc positivity without becoming carrier or ill. Long-term protection against HBV by vaccination appears to be excellent.

Modelling long-term persistence of hepatitis B antibodies after vaccination.

Antibody response to hepatitis B vaccination was measured in 97 institutionalized, mentally handicapped patients after a 0-, 1-, 6-month vaccination schedule. Two groups were formed at month 7 according to the antibody response, which determined whether they needed an additional vaccine dose at month 12, to achieve an antibody titre of 100 IU/liter. All residents were followed up yearly for the first 5 years, after which, they received another booster dose. Another blood sample was taken 11 years after the start of the program. A linear mixed-regression model was used to analyze the data. Random and fixed effects were included to determine the generally known risk factors and the still unknown individual characteristics that influence the titre of hepatitis B surface antibodies (anti-HBs). The mean anti-HBs titre was a function of time, type of mental retardation (Down's syndrome or other types of mental retardation), the use of antiepileptic drugs, and the additional booster at month 12. The immediate and vigorous response of the immune system to booster vaccination shows that the immunologic memory is good after primary vaccination. For the maintenance of protection, the recommendation for mentally retarded patients in institutions is vaccination of all seronegative residents as well as new entrants, after which, no additional boosters will be necessary.